I2-Catalyzed Oxidative Coupling of Ketone Oximes and Dialkyl/Diarylphosphine Oxides

Article abstract of DOI:10.1055/s-0040-1707306

A new protocol for the oxidative coupling of ketone oximes with dialkyl/diarylphosphine oxides to synthesize O -(dialkylphosphinyl)ketone oximes has been developed. Hydrogen peroxide is used as a green oxidizing agent, and molecular iodine is used as a nonmetal catalyst. The reaction has a high atom economy, with water as the only byproduct. O -(Dialkylphosphinyl)ketone oximes with 26 examples have been obtained with high yields. Furthermore, the product may be transformed into other molecules, i.e., by reduction.

Full text of DOI:10.1055/s-0040-1707306

SYNLETT
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 32, 75–80
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75
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N. Li et al.
Letter
Synlett
I2-Catalyzed Oxidative Coupling of Ketone Oximes and Dialkyl/
Diarylphosphine Oxides
Nutao Li
OH
N
5 mol% I2
1.2 equiv H2O2
O
N
O
P
H
Y
R2
Y
Yiding Wang
Hongqin Yang
Ze He
P
R2
R2
+
R1
R2
O
R1
Y = CH=CH, S, O
MeCN, 40 °C, 4 h
26 examples
63~93% yields
· mild, green, efficient process
· water as byproduct
· transition-metal-free catalysis
Qingle Zeng*
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7
5
0
-5
4
0
X
State Key Laboratory of Geohazard Prevention and
Geoenvironment Protection, College of Materials,
Chemistry & Chemical Engineering, Chengdu Universi-
ty of Technology, Chengdu 610059, P. R. of China
qinglezeng@hotmail.com
Corresponding Author
Received: 08.08.2020
Accepted after revision: 31.08.2020
Published online: 08.10.2020
synthesizing O-(dialkylphosphinyl)ketone oxime and phos-
phonate oxime ester is also often used by chemists as a
template reaction for surfactant efficiency detection.9 The
introduction of phosphorus atoms into oxime molecules
has become an interesting research topic, although O-(dial-
kylphosphinyl)ketone oximes are still underdeveloped mol-
ecules.
DOI: 10.1055/s-0040-1707306; Art ID: st-2020-v0440-l
Abstract A new protocol for the oxidative coupling of ketone oximes
with dialkyl/diarylphosphine oxides to synthesize O-(dialkylphos-
phinyl)ketone oximes has been developed. Hydrogen peroxide is used
as a green oxidizing agent, and molecular iodine is used as a nonmetal
catalyst. The reaction has a high atom economy, with water as the only
byproduct. O-(Dialkylphosphinyl)ketone oximes with 26 examples have
been obtained with high yields. Furthermore, the product may be trans-
formed into other molecules, i.e., by reduction.
N
N
N
N
N
N
O
O
O
O
O
P
P
P
Key words ketone oximes, di[alkyl/(hetero)aryl]phosphine oxides, O-
(dialkylphosphinyl)ketone oximes, oxidative coupling, molecular iodine,
synthetic method
O
O
O
O
O
DOEPBI
DPPBI
DOPPBI
In recent years, oximes have increasingly been applied
as bioactive agents and drugs, such as fungicides, antispas-
modics, anticonvulsants, and antivirals.1 Oxime derivatives
also play an important role in organic reactions. For exam-
ple, ketoxime derivatives can generate imine radicals under
the action of transition metals Cu(I), Cr(II),2 or by photooxi-
dation reduction.3 In addition, oxime derivatives are also
used as 1,3-dipoles,4 electrophiles and nucleophiles,5 and
protecting groups for carbonyl compounds.6 Among various
organic compounds containing phosphorus, phosphonates
are a key component of polymer science and biologically
active compounds.7 Among the many derivatives of ketox-
ime, compounds containing N–O–P bonds (for example, O-
(dialkylphosphinyl)ketone oxime, phosphonic acid oxime
ester) are widely used in organic synthesis, life science,
polymer science, and pharmaceutical fields. This type of
compound has been shown to generate nitrogen cations for
related reactions through the cleavage of the N–O bond. It is
also an excellent organophosphorus coupling reagent. For
example, it plays an important role in the research on pep-
tide chain synthesis (Figure 1).8 In addition, the reaction of
Figure 1 Organophosphorus reagent for synthesizing peptide chain
The formation of O–P bonds from oximes and organo-
phosphorus compounds has received much research atten-
tion. The classical synthesis of O-(dialkylphosphinyl)ketone
oximes involves the condensation of ketone oximes with
chlorodialkylphosphine oxide (Scheme 1, eq. A);10 Further-
more, Harger has used diphenylhydroxylamine and acetone
to obtain the same product (Scheme 1, eq. B);10 Sokolov has
used chloronitroso compounds and diisobutylphosphorus
chloride or diphenyl(trimethylsilyl)phosphine oxide to ob-
tain the corresponding dialkyl phosphine oxide esters un-
der the action of sulfur dioxide (Scheme 1, eq. C);11,12 Wu
has used oximes, diethyl phosphite, excess toxic and ozone-
depleting tetrachloromethane, and excess triethylamine to
synthesize oxime phosphates using the Atherton–Todd re-
action (Scheme 1, eq. D);13 Hashemi has used oximes and
trialkyl phosphites to produce decyl phosphites under the
action of azodiisopropyldicarboxylate (Scheme 1, eq. E).14
© 2020. Thieme. All rights reserved. Synlett 2021, 32, 75–80
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

76
N. Li et al.
Letter
Synlett
system has been reported to be suitable for some oxidative
coupling reactions.19 Adding 10 mol% molecular iodine im-
proved the reaction (entries 5 vs. 3). Screening of the reac-
tion time showed that 4 h was sufficient (entries 6 and 7).
Furthermore, the preferred amount of H2O2 was 1.2 equiv
(entries 7–9), while the amount of catalyst I2 could be de-
creased to 5 mol% (entries 10 and 11). A small excess of di-
phenylphosphine oxide (2a) was also beneficial (entry
12).20,21
A: previous work: ref. 10
O
benzene
r.t, 05 h
Ph
O
OH
+
Ph
P
Ph
P
N
N
Ph
Cl
O
B: previous work: ref. 10
O
benzene
r.t, 05 h
Ph
O
+
Ph
P
Ph
P
N
O
Ph
O
O
NH2
C: previous work: ref. 11,12
O
R
SO2
O
N
CCl2
R
(i-Bu)2PCl
+
(i-Bu)2
P
O
O
N
C
C
H
– SOCl2
Cl
Ar
Table 1 Screening of Reaction Conditionsa
Ar
Ar
Ph2POSiMe3
+
R
N O
Ph2PON
– ClSiMe3
Cl
D: previous work: ref. 13
R1
R2
N
OH
O
R2
N
O
O
O
solvent, oxidant
T (°C), t (h)
CCI4, Et3N
r.t
N
P
+
P
H
O
+
O
P
O
P
H
HO
R1
O
O
N
O
E: previous work: ref. 14
1a
2a
3a
R
O
N
OH
DIAD, C2H4Cl2
r.t, 10 h
OR
+ P(OR)
R
N
P
O
Entry Solvent
Temp
Oxidant
(equiv)
Catalyst
(%)
Time
(h)
Yield 3a
(%)
OR
(°C)
R = Me, Et
This work:
1
2
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
25
40
40
40
40
40
40
40
40
40
40
40
25
air
–
–
–
–
12
12
12
12
12
2
35
39
71
56
85
75
85
81
85
79
85
88
44
OH
N
R2
O
N
O
Y
Y
1.2 equiv H2O2, 5 mol% I2
MeCN, 40 °C, 4 h
air
P
R2
P
H
R2
R2
R1
+
R1
O
3
H2O2 (1.2)
TBHP (1.2)
H2O2 (1.2)
H2O2 (1.2)
H2O2 (1.2)
H2O2 (1.0)
H2O2 (1.5)
H2O2 (1.2)
H2O2 (1.2)
H2O2 (1.2)
–
Y = CH=CH, S, O
· the only byproduct is water
· green oxidant
· metal-free catalysis
· mild conditions
26 examples
63–93% yields
4
5
I2 (10)
6
I2 (10)
I2(10)
I2 (10)
I2 (10)
I2 (2)
I2 (5)
I2 (5)
–
Scheme 1 Synthetic methods for O-(dialkylphosphinyl)ketone oximes
7
4
8
4
Although several methods for the synthesis of O-(dial-
kylphosphinyl)ketone oximes have been reported, most use
ozone-depleting and toxic halogen-substituted reagents,
such as chlorodiphenylphosphine oxide, chloronitroso com-
pounds, dichloroethane, and carbon tetrachloride.10–14
These substances are harmful to the environment. Further-
more, the use of organic intermediates with higher activity
in another part of the reaction greatly increases the reac-
tion cost.15,16
9
4
10
11
4
4
12b MeCN
13c
CCl4/Et3N
4
5
a Unless otherwise mentioned, the reaction was carried out with 1a (0.5
mmol), 2a (0.5 mmol), 30% aqueous H2O2, solvent (2 mL), 12 h, in air. Isolat-
ed yield.
b The reaction was carried out at 1a (0.5 mmol) and 2a (0.6 mmol).
c The reaction was carried out at 1a (0.5 mmol) and 2a (0.5 mmol), triethyl-
amine (0.5 mL), and CCl4 (2 mL).
As part of our ongoing study on oxidative coupling17 and
green chemistry,18 we report herein the development of a
simple, highly efficient, highly atom economical, and green
method for the synthesis of O-(dialkylphosphinyl)ketone
oximes from ketone oximes and dialkyl/(hetero)aryl phos-
phine oxides using iodine as catalyst and hydrogen perox-
ide as oxidant (Scheme 1).
First, 1-indanone oxime (1a) and diphenylphosphine
oxide (2a) were used as model substrates to screen reaction
conditions (Table 1). Interestingly, the oxidative coupling
reaction occurred in air, although the yield was only 35%
(Table 1, entry 1), while increasing the temperature to 40 °C
gave a slightly higher yield (entry 2). Adding aqueous H2O2
or tert-butyl hydroperoxide (TBHP) as oxidants greatly pro-
moted the oxidative coupling (entries 3 and 4). The I2/H2O2
The reaction of oximes with diethyl phosphonates un-
der Atherton–Todd reaction conditions has been reported
to give oxime phosphates in high yields.13 However, the re-
action of 1-indanone oxime with diphenylphosphine oxide
under the reported conditions afforded a low yield (Table 1,
entry 13). This result suggested that the Atherton–Todd re-
action system was not suitable for diarylphosphine oxides.
Use of ozone-depleting and toxic CCl4 also demonstrate the
defect of the Atherton–Todd reaction.
With the optimized reaction conditions in hand, various
ketone oximes 1 were evaluated in the reaction with di-
phenylphosphine oxide (2a, Scheme 2).
© 2020. Thieme. All rights reserved. Synlett 2021, 32, 75–80

77
N. Li et al.
Letter
Synlett
N
OH
O
MeCN, H2O2, I2
40 °C, 4 h
N
O
P O
(Y)
+
P
H
(Y)
Y = CH=CH, S, O
1
2a
3
N
O P O
N
O P O
N
O P O
N
O
P
O
Br
Cl
F
3a, 88%
3b, 90%
3c, 87%
3d, 84%
N
O P O
N
O P O
N
O P O
N
O P O
O
O
3e, 89%
3f, 83%
3g, 91%
3h, 93%
N
O P O
N
O
P
O
N O P O
N
O P O
O
F
F3C
F
3i, 85%
3j, 90%
3k, 80%
3l, 81%
N
O P O
N
N
O P O
O
P
O
N
O
P
O
O
S
3m, 86%
3n, 63%
3o, 83%
3p, 84%
Scheme 2 Reaction of various ketone oximes (1) and diphenylphosphine oxide (2a). Reagents and conditions: 1 (0.5 mmol), 2a (0.6 mmol), 30% aque-
ous H2O2 (0.6 mmol), I2 (0.025 mmol), CH3CN (2 mL), 40 °C, 4 h, in air. Isolated yield.
All acetophenone oximes and 1-indanone oximes af-
forded good to excellent yields of 80–93% (3a–l), regardless
of whether the benzene ring substituent was an electron-
withdrawing (halo, trifluoromethyl) or an electron-donat-
ing group (methoxyl, methyl). Furthermore, no clear trends
were observed regarding the effect of electron-donating
and electron-withdrawing groups on the aromatic ketone
oximes on the reaction yield.
Dialkyl ketone oximes and alkyl heteroaryl ketone ox-
imes also reacted smoothly with diphenylphosphine oxide.
The reaction using 3-methylbutan-2-one oxime afforded
product 3m in good yield, while cyclopentanone oxime
gave only a moderate yield of 3n (63%). Pleasingly, both
thienyl and furyl ketone oximes afforded satisfactory re-
sults (3o and 3p). The presence of heteroatoms did not
seem to impede the reaction.
Reactions of various di[(hetero)aryl/alkyl] phosphine
oxides 2 with 1-indanone oxime (1a) were also screened
(Scheme 3). All di[(hetero)aryl/alkyl] phosphine oxides 2
afforded good to excellent yields (3a,q–z). For diarylphos-
phine oxides (3q–x), the electronic influence of substitu-
ents on the reaction seemed to be relatively small com-
pared with the effect of their position on the benzene ring:
ortho-substituents clearly inhibited the reaction (3v vs. 3u),
while meta substituents have some influence on the oxida-
tive coupling (3q vs. 3r; 3u vs. 3t; 3x vs. 3w). Importantly,
other phosphine oxides, such as di(2-thienyl)phosphine ox-
ide and dicyclopentylphosphine oxide, were also well toler-
ated in the reaction, affording good yields (3y–z).
To verify the possibility of scale-up using this method,
the reaction was conducted on a gram scale (Scheme 4). Re-
acting 1a (10 mmol) and 2a (12 mmol) under the optimized
© 2020. Thieme. All rights reserved. Synlett 2021, 32, 75–80

78
N. Li et al.
Letter
Synlett
R2
O
N
OH
O
P
I2, H2O2
N
R2
+
R2
P
H
R2
O
3 equiv NaBH4, 2 mL EtOH
60 °C, 6 h
O
P
O
N
N
P
MeCN, 40 °C, 4 h
O
O
H
3
2
1a
3a
4, 87%
F
P
F
Scheme 5 Transformation of the product 3a by reduction with NaBH4
F
N
O
O
N
O
P
O
N O P O
drous ethanol as solvent, reduced product 4 was successful-
ly obtained in 87% yield after reacting for 6 h at 60 °C.22,23
To study the reaction mechanism, the following control
experiments were performed (Scheme 6). A free-radical
trapping experiment was also conducted (Scheme 6, eq. 1).
Adding 3 equiv of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl
(TEMPO) to the reaction under the optimized conditions
gave 3a in 79% yield, which was similar to the yield of the
template reaction. This result indicated that the reaction
did not occur via a free-radical pathway.
F
3a, 88%
3q, 82%
3r, 85%
O
Cl
O
O
N
O
P
O
N
O
P
O
N
O P O
O
Cl
1.2 equiv H2O2
5 mol% I2
N
OH
3t, 87%
3u, 81%
3s, 83%
O
O
O
(1)
+
Ph
P
H
Ph
N
P
2 mL MeCN, 40 °C, 4 h
3 equiv TEMPO
Ph Ph
3a, 79%
1a
2a
O
N
O P O
N
O P O
N
O P O
1.2 equiv H2O2
1 equiv I2
O
O
P
I
O
(2)
P
H
2 mL MeCN, 40 °C, 4 h
2a
5
3x, 72%
31P NMR: 21.52 ppm
31P NMR: 32.06 ppm
3v, 76%
3w, 81%
Scheme 6 Control experiments
S
N
O
P O
N
O P O
A mixture of diphenylphosphine oxide and 1 equiv of
molecular iodine was stirred under the optimized reaction
conditions for 4 h (Scheme 6, eq. 2). The resulting mixture
was condensed using a rotary evaporator, dissolved in CDCl3,
and analyzed by 31P NMR (see the Supporting Information).
The results showed 31P NMR peaks at  = 32.06 ppm. Ac-
cording to the literature, the peak at  = 32.06 ppm is as-
signed to iododiphenylphosphorus oxide Ph2P(O)I (5).24
This result suggested that iododiphenylphosphine oxide (5)
was the active intermediate in this reaction.
Based on the above experimental studies, we have pro-
posed a possible mechanism (Scheme 7). First, the nucleo-
philic tautomer hydroxydiphenylphosphine 4 readily attacks
readily polarizable I2 to form active intermediate 6.25 Inter-
mediate 6 releases HI and is converted into active nucleo-
philic agent iododiphenylphosphine oxide 5. Intermediate 5
then undergoes nucleophilic substitution with ketoxime 1
to form target product 3 and one molecule of HI. HI is oxi-
dized to molecular iodine, which takes part in a new cycle.
In this process, water is produced as the only byproduct.
In summary, O-(dialkylphosphinyl)ketone oximes have
potential applications as biologically active compounds.
This study provides a green and efficient method for the
synthesis of such compounds, reporting 26 examples. This
S
3y, 75%
3z, 79%
Scheme 3 Reaction of various di[(hetero)aryl/alkyl] phosphine oxides
2 with 1-indanone oxime (1a). Reagents and conditions: 1a (0.5 mmol),
2 (0.6 mmol), 30% aqueous H2O2 (0.6 mmol), I2 (0.025 mmol), CH3CN
(2 mL), 40 °C, 4 h, in air. Isolated yield.
N
OH
O
O
MeCN, H2O2, I2
40 °C, 4 h
N
P
O
+
P
H
1a, 10 mmol
2a, 12 mmol
3a, 83%, 2.88 g
Scheme 4 Gram-scale reaction
reaction conditions afforded target product 3a in 83% yield
(2.88 g).
To explore the further transformation of these reaction
products, the reduction of O-(diphenylphosphinyl)inda-
none oxime (3a) was performed (Scheme 5). Using 3 equiv
of sodium borohydride as the reducing agent and anhy-
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79
N. Li et al.
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(6) (a) Chen, X.; Dam, M. A.; Ono, K.; Mal, A.; Shen, H. S. R.; Sheran,
N. K.; Wudl, F. A. Science 2002, 295, 1698. (b) Obadia, M. M.;
Mudraboyina, B. P.; Serghei, A.; Montarnal, D.; Drockenmuller,
E. J. Am. Chem. Soc. 2015, 137, 6078. (c) Scott, T. F.; Schneider, A.
D.; Cook, W. D.; Bowman, C. N. Science 2005, 308, 1615.
(7) Ouattara, M.; Wein, S.; Calas, M.; Hoang, Y. V.; Vial, H.; Escale, R.
Med. Chem. Lett. 2007, 17, 593.
(8) El-Faham, A.; Khattab, S. N.; Subirós-Funosas, R.; Albericio, F.
J. Pept. Sci. 2013, 20, 1.
(9) Gupta, B.; Sharma, R.; Singh, N.; Karpichev, Y.; Satnami, M. L.;
Ghosh, K. K. J. Phys. Org. Chem. 2013, 26, 632.
O
OH
P
R2
P
R2
R2
R2
H2O
H
I2
4
2
H2O2
I–
OH
R2
P
R2
HI
O
R2
O
I
6
N
P
Y
R2
R1
O
3
R2
P
R2
(10) Harger, M. J. P. J. Chem. Soc., Perkin Trans. 1 1981, 3284.
(11) Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V. Bull.
Acad. Sci. USSR Div. Chem. Sci. 1987, 36, 2401.
I
5
N
OH
Y
R1
(12) Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Goreva, T. V.;
Martynov, I. V. Bull. Acad. Sci. USSR Div. Chem. Sci. 1990, 39, 413.
(13) Wu, S. M.; Zhang, X. H. J. Chem. Res. 2007, 3, 146.
1
Scheme 7 A proposed mechanism
(14) Hashemi, S. A.; Khalili, G. Monatsh. Chem. 2015, 146, 965.
(15) Zhu, J.-L.; Wu, S.-T.; Shie, J.-Y. J. Org. Chem. 2014, 79, 3623.
(16) Russell, G. A.; Ros, F.; Hershberger, J.; Tashtoush, H. J. Org. Chem.
1982, 47, 1480.
(17) (a) Jiang, W.; Huang, Y.; Zhou, L.; Zeng, Q. Sci. China Chem. 2019,
62, 1213. (b) Yang, L.; Feng, J.; Qiao, M.; Zeng, Q. Org. Chem.
Front. 2018, 5, 24. (c) Zheng, W.; Tan, M.; Yang, L.; Zhou, L.;
Zeng, Q. Eur. J. Org. Chem. 2020, 1764. (d) Tan, M.; Zheng, W.;
Yang, L.; Zhou, L.; Zeng, Q. Asian J. Org. Chem. 2019, 8, 2027.
(18) (a) Kuchukulla, R. R.; Li, F.; Zhou, L.; He, Z.; Zeng, Q. Green Chem.
2019, 21, 5808. (b) Jiang, W.; Li, N.; Zhou, L.; Zeng, Q. ACS Catal.
2018, 8, 9899. (c) Zhang, L.; Tan, M.; Zhou, L.; Zeng, Q. Tetrahe-
dron Lett. 2018, 59, 2778.
process shows good merits, including using hydrogen per-
oxide as oxidant and molecular iodine as catalyst, easy op-
eration in air, high atom economy, mild conditions, and wa-
ter as the only byproduct. According to our experimental
results and related reports, a mechanism was proposed for
this molecular iodine-catalyzed oxidative cross-coupling
reaction.
Funding Information
(19) (a) Vessally, E.; Didehban, K.; Mohammadi, R.; Hosseinian, A.;
Babazadeh, M. J. Sulfur Chem. 2018, 39, 332. (b) Detty, M. R.;
Zhou, F.; Friedman, A. E. J. Am. Chem. Soc. 1996, 118, 313.
(c) Huang, H.-M.; Li, Y.-J.; Ye, Q.; Yu, W.-B.; Han, L.; Jia, J.-H.; Gao,
J.-R. J. Org. Chem. 2014, 79, 1084. (d) Pavlinac, J.; Zupan, M.;
Stavber, S. J. Org. Chem. 2006, 71, 1027.
This work was supported by the State Key Laboratory of Geohazard
Prevention and Geoenvironment Protection (SKLGP2018Z002).
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n
(S
K
L
G
P
2
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1
8
Z
0
0
2)
Supporting Information
Supporting information for this article is available online at
(20) General Procedure for I2-Catalyzed Oxidative Coupling of
Ketone Oximes and Dialkyl/Diarylphosphine Oxides
A 25 mL test tube equipped with a magnetic stirrer was charged
with ketone oxime (0.5 mmol), dialkyl/diarylphosphine oxide
(0.6 mmol), H2O2 (0.6 mmol), I2 (5 mol%) and acetonitrile (2
mL). After the test tube was directly sealed in air with a sleeve
stopper septum, the reaction mixture was stirred at 40 °C for 4
h in air. After cooled to room temperature, the reaction mixture
was quenched by the addition of saturated Na2S2O3 solution (10
mL). The reaction mixture was extracted with ethyl acetate (3 ×
15 mL). The combined organic phase was dried over MgSO4, fil-
tered, and concentrated in vacuum on a rotary evaporator. The
resulting residue was purified by silica gel flash chromatogra-
phy, eluting with EtOAc/petroleum ether (3:7 to 5:5), to afford
the desired products 3.
https://doi.org/10.1055/s-0040-1707306.
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References and Notes
(1) (a) Davies, J.; Morcillo, S. P.; Douglas, J. J.; Leonori, D. Chem. Eur.
J. 2018, 24, 12154. (b) Rosa, L. D.; Stasi, R. D.; Longhitano, L.;
D’Andrea, L. D. Bioorg. Chem. 2019, 91, 103160. (c) Liu, W.-X.;
Zhang, C.; Zhang, H.; Zhao, N.; Yu, Z.-X.; Xu, J. J. Org. Chem. 2017,
139, 8678.
(2) (a) Ren, Z.-H.; Zhang, Z.-Y.; Yang, B.-Q.; Wang, Y.-Y.; Guan, Z.-H.
Org. Lett. 2019, 13, 5394. (b) Takai, K.; Katsura, N.; Kunisada, Y.
Chem. Commun. 2001, 1724. (c) Corey, E. J.; Richman, J. E. J. Am.
Chem. Soc. 1970, 92, 5276.
(3) (a) Peng, J.; Zhi, P.; Yuan, Z.; Dan, S.; Hao, Y.; Xiao, Q.; Huang, Y.
Org. Lett. 2019, 21, 2658. (b) Zard, S. Z. Chem. Soc. Rev. 2008, 37,
1603.
(4) (a) Hirata, Y.; Nakamura, S.; Watanabe, N.; Kataoka, O.;
Kurosaki, T.; Anada, M.; Hashimoto, S. Chem. Eur. J. 2006, 12,
8898. (b) Eckelbarger, J. D.; Wilmot, J. T.; Gin, D. Y. J. Am. Chem.
Soc. 2006, 128, 10370. (c) Maggini, M.; Scorrano, G.; Prato, M.
J. Am. Chem. Soc. 1993, 115, 9798.
(21) Analytical Data for O-(diphenylphosphinoyl)-5-fluoro-1-
indanone oxime (3b)
White solid (164 mg, 90%); mp 171–174 °C. 1H NMR (400 MHz,
CDCl3):  = 7.89 (ddd, J = 12.3, 8.3, 1.4 Hz, 4 H), 7.63 (dd, J = 8.6,
5.3 Hz, 1 H), 7.58–7.52 (m, 2 H), 7.51–7.40 (m, 4 H), 6.99 (dd, J =
8.7, 2.2 Hz, 1 H), 6.92 (td, J = 8.8, 2.4 Hz, 1 H), 3.21–3.13 (m, 2 H),
3.11–2.98 (m, 2 H). 13C NMR (101 MHz, CDCl3):  = 170.54,
170.42, 166.57, 164.06, 152.06, 151.97, 132.31, 132.28, 132.14,
132.04, 131.40, 130.50, 130.04, 128.55, 128.41, 124.93, 124.83,
115.27, 115.04, 112.45, 112.23, 28.42, 28.40, 28.17. 31P NMR
(162 MHz, CDCl3):  = 34.93. HRMS (ESI-TOF): m/z [M + H]+
(5) (a) Feng, X.-H.; Zhang, G.-Z.; Chen, C.-Q.; Yang, M.-Y.; Xu, X.-Y.;
Huang, G.-S. Synth. Commun. 2009, 39, 1768. (b) Kumar, S. C. S.;
Kumar, N. V.; Srinivas, P.; Bettadaiah, B. K. Synthesis 2014, 46,
1847.
© 2020. Thieme. All rights reserved. Synlett 2021, 32, 75–80

80
N. Li et al.
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Synlett
calcd for C21H18FNO2P: 366.1059; found: 366.1066. HRMS (ESI-
TOF): m/z [M + Na]+ calcd for C21H17FNO2NaP: 388.0878; found:
388.0851.
(23) Analytical
Data
for
{[(2,3-Dihydro-1H-inden-1-
yl)amino[oxy}diphenylphosphine Oxide (4)
White solid (151 mg, 87%); mp 141–144 °C. 1H NMR (400 MHz,
CDCl3) δ = 7.95–7.83 (m, 4 H), 7.66 (d, J = 7.8 Hz, 1 H), 7.54 (td,
J = 7.5, 1.2 Hz, 2 H), 7.47 (td, J = 7.4, 3.6 Hz, 4 H), 7.38 (t, J = 7.2
Hz, 1 H), 7.32 (d, J = 7.6 Hz, 1 H), 7.21 (t, J = 7.4 Hz, 1 H), 3.15
(dd, J = 7.8, 4.0 Hz, 2 H), 3.12–3.04 (m, 2 H). 13C NMR (101 MHz,
CDCl3) δ = 171.81, 171.69, 149.52, 134.43, 132.25, 132.23,
132.16, 132.06, 131.79, 131.51, 130.16, 128.52, 128.39, 127.08,
125.57, 123.20, 30.20, 29.71, 28.40, 27.77. 31P NMR (162 MHz,
CDCl3) δ = 29.54. HRMS (ESI-TOF) m/z: [M+H]+ calcd for C21H21-
NO2P [M+H]+ 350.1309; found: 350.1895.
(22) Procedure for the Reduction of O-(Diphenylphosphino)inda-
none Oxime (3a)
A 25 mL test tube equipped with a magnetic stirrer was charged
with O-(diphenylphosphinyl)indanone oxime (3a, 1 mmol) and
sodium borohydride (3 mmol), acetonitrile (2 mL). After the test
tube was directly sealed in air with a sleeve stopper septum, the
reaction mixture was stirred at 60 °C for 6 h in air. After cooled
to room temperature, the reaction mixture was quenched by
the addition of saturated NaCl solution (10 mL). The reaction
mixture was extracted with ethyl acetate (3 × 15 mL). The com-
bined organic phase was dried over MgSO4, filtered, and con-
centrated in vacuum on a rotary evaporator. The resulting
residue was purified by silica gel flash chromatography, eluting
with EtOAc/petroleum ether (3:7), to afford the desired product 4.
(24) Kawaguchi, S.-i.; Ogawa, A. Org. Lett. 2010, 12, 1893.
(25) Hosseinian, A.; Farshbaf, S.; Fekri, L. Z.; Nikpassand, M.; Vessally,
E. Curr. Top. Med. Chem. 2018, 376, 23.
© 2020. Thieme. All rights reserved. Synlett 2021, 32, 75–80